Review of hyperbilirubinemia and Bilirubin-induced neurologic damage

1. Le Pichon JB, Riordan SM, Watchko J, Shapiro SM. The Neurological Sequelae of Neonatal Hyperbilirubinemia: Definitions, Diagnosis and Treatment of the Kernicterus Spectrum Disorders (BINDs). Curr Pediatr Rev. 2017. 13(3):199-209.
2. Bhutani VK, Wong RJ, Stevenson DK. Hyperbilirubinemia in Preterm Neonates. Clin Perinatol. 2016. Jun;43(2):215-32.
3. Watchko JF and Tiribelli C. Bilirubin-induced-neurologic-damage – Mechanisms and management approaches. N Engl J Med. 2013. 3691:2021-30.
4. Olusanya BO, Teeple S, Kassebaum NJ. The Contribution of Neonatal Jaundice to Global Child Mortality: Findings from the GBD 2016 Study. Pediatrics. 2018. Feb;141(2).
5. Das S and Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Mar; 9(1): 24.
6. Cayabyab and Ramanathan. High unbound bilirubin effects on the developing brain. Pediatric Research (2019) 85:183–190

Current clinical management of neonatal hyperbilirubinemia

1. American Academy of Pediatrics. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004. 114:297.
2. Maisels et al. An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestation. J Perinatol. 2012; 32:660.
3. Kuzniewicz MW, Escobar GJ, Newman TB. Impact of universal bilirubin screening on severe hyperbilirubinemia and phototherapy use. Pediatrics. 2009 Oct;124(4):1031-9.
4. Bhutani VK , Meng VK, Knauer Y, Danielsen BH, Wong RJ, Stevenson1DK and Gould JB. Extreme hyperbilirubinemia and rescue exchange transfusion in California from 2007 to 2012. J of Perinatology (2016) 36, 853–857.

Challenges of using BT as a clinical diagnostic test

1. Holtzman NA. Management of hyperbilirubinemia: quality of evidence and cost. Pediatrics. 2004. Oct;114(4):1086-8.
2. Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM. Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns. Pediatrics. 2006. Feb;117(2):474- 85.
3. Ahlfors CE. Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr. 2010 Apr;22(2):129-33.
4. Watchko JF, Maisels MJ. The enigma of low bilirubin kernicterus in premature infants: why does it still occur, and is it preventable? Semin Perinatol 2014. 38:397.
5. Das S and Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Mar; 9(1): 24.

Adverse effects associated with of phototherapy

1. Morris BH, Oh W, Tyson JE, Stevenson DK,et al.; NICHD Neonatal Research Network Aggressive vs. conservative phototherapy for infants with extremely low birth weight. N Engl J Med. 2008. Oct 30;359(18):1885-96.
2. Newman TB, Wu YW, Kuzniewicz MW, Grimes BA, McCulloch CE. Childhood Seizures After Phototherapy. Pediatrics. 2018. Oct;142(4).
3. Newman 2016 Phototherapy and Childhood Cancer. Pediatrics. 2016. 137(6)
4. Wickremasinghe AC, Kuzniewicz MW, Grimes BA, McCulloch CE, Newman TB. Neonatal Phototherapy and Infantile Cancer. Pediatrics. 2016 Jun;137(6).
5. Muchowski K et al. Evaluation and Treatment of Neonatal Hyperbilirubinemia. American Academy of Family Physician. 2014 89(11)
6. Watchko JF. Measurement of Circulating Unbound Bilirubin: Will It Ever Be a Part of Routine Neonatal Care? J Pediatrics. 2016; 173:6

Free bilirubin is a better predictor for Bilirubin-induced-neurologic-damage and its clinical application

1. Funato M, Tamai H, Shimada S and Nakamura H. Vigintiphobia, Unbound Bilirubin, and Auditory Brainstem Responses. Pediatrics January 1994, 93 (1) 50-53.
2. Amin SB, Ahlfors C, Orlando MS, Dalzell LE, Merle KS, Guillet R. Bilirubin and serial auditory brainstem responses in premature infants. Pediatrics. 2001 Apr;107(4):664-70.
3. Ahlfors CE and Parker AE. Unbound Bilirubin Concentration is Associated With Abnormal Automated Auditory Brainstem Response for Jaundiced Newborns. Pediatrics. 2008 May;121(5):976-8.
4. Ahlfors CE, Amin SB, Parker AE. Unbound bilirubin predicts abnormal automated auditory brainstem response in a diverse newborn population. J Perinatol. 2009 Apr;29(4):305-9
5. Morioka I, Nakamura H, KodaT, Sakai H, Kurokawa H, Yonetani M, et al. Serum unbound bilirubin as a predictor for clinical kernicterus in extremely low birth weight infants at a late age in the neonatal intensive care unit. Brain Dev. 2015 Sep;37(8):753-7.
6. Amin Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice. J Pediatrics; 2016;73:84-88.
7. Amin SB, Saluja S, Saili A, Orlando M, Wang H, Laroia N, Agarwal A. Chronic Auditory Toxicity in Late Preterm and Term Infants With Significant Hyperbilirubinemia. Pediatrics. 2017; Oct;140(4).
8. Amin SB and Wang H. Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants. J Pediatr. 2018 Jan;192:47-52.
9. van der Schoor LWE, Dijk PH, Verkade HJ, Kamsma ACJ, Chreuder AB, Groen H. et al. Unconjugated free bilirubin in preterm infants. Early Human Development 2017 (106–107: 25–32.
10. Morioka I. Hyperbilirubinemia in preterm infants in Japan: New treatment criteria. Pediatrics International. 2018; 60:684 –690.

Measurement of free bilirubin: Peroxidase method, the gold standard

1. Jacobsen J, and Wennberg RP. Determination of unbound bilirubin in the serum of newborns. Clin Chem 1974;20:783.
2. Nakamura H. glucose peroxidase method. Clinical. Chem Acta. 1977; 79:411-417

New concepts of bilirubin binding affinity and capacity

1. Ahlfors CE. The Bilirubin Binding Panel: A Henderson-Hasselbalch Approach to Neonatal Hyperbilirubinemia. Pediatrics. 2016. Oct;138(4).
2. Ahlfors CE, Bhutani VK, Wong RJ, Stevenson DK. Bilirubin binding in jaundiced newborns: from bench to bedside? Pediatr Res 2018. 84:494.
3. Wennberg RP. Commentary: Bench to bedside–one step closer? Pediatr Res. 2018 Oct;84(4):483- 484.